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Vaccine. 2014 Oct 29;32(47):6266-76. doi: 10.1016/j.vaccine.2014.09.010. Epub 2014 Sep 19.

Loading dendritic cells with PLA-p24 nanoparticles or MVA expressing HIV genes induces HIV-1-specific T cell responses.

Author information

1
Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain; AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain. Electronic address: ncliment@clinic.ub.es.
2
Institut de Biology et Chimie des Protéines, UMR5305, UCBL, 7 Passage du Vercors, 69367 Lyon Cedex 07, France.
3
Department of Microbiology and Parasitology, Pharmacy Faculty, Universitat de Barcelona, Barcelona, Spain.
4
AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain; Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Barcelona, Spain.
5
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
6
Service of Immunology, Hospital Clínic de Barcelona, Barcelona, Spain; AIDS Research Group, and Catalonian Center for HIV Vaccines (HIVACAT), Barcelona, Spain.

Abstract

Since recent data suggest that nanoparticles and modified vaccinia ankara (MVA) vectors could play a pivotal role in HIV-1 therapeutics and vaccine design, in an ex vivo model of human monocyte-derived dendritic cells (MDDCs), we compared two different loading strategies with HIV-1 vaccine vehicles, either viral or synthetic derived. We used polylactic acid (PLA) colloidal biodegradable particles, coated with HIV Gag antigens (p24), and MVA expressing Gag (rMVA-gag and rMVA-gag/trans membrane) or Tat, Nef and Rev genes (rMVA tat+rev and rMVA nef). PLA-p24 captured by MDDCs from HIV-1 individuals induced a slight degree of MDDC maturation, cytokine and chemokine secretion and migration towards a gradient of CCL19 chemokine and highly increased HIV-specific CD8(+) T-cell proliferation compared with p24 alone. After complete maturation induction of PLA-p24-pulsed MDDCs, maximal migration towards a gradient of CCL19 chemokine and induction of HIV-specific T-cell proliferation (two-fold higher for CD4(+) than CD8(+)) and cytokine secretion (IFN-γ and IL-2) in the co-culture were observed. Upon exposure to MVA-gag, MDDCs produced cytokines and chemokines and maintained their capacity to migrate to a gradient of CCL19. MDDCs infected with MVA-gag and MVA-gag trans-membrane were able to induce HIV-specific CD8(+) proliferation and secretion of IFN-γ, IL-2, IL-6 and TNF-α. We conclude that both HIV antigens loading strategies (PLA-p24 nanoparticles or MVA expressing HIV genes) induce HIV-1-specific T-cell responses, which are able to kill autologous gag-expressing cells. Thus, they are plausible candidates for the development of anti-HIV vaccines.

KEYWORDS:

Cytokines; HIV core protein p24; HIV immunogens; Human CD4(+) T and CD8(+) T-cells; Human monocytes derived-dendritic cells; MVA; Polylactic acid (PLA) particles; Proliferation

PMID:
25240755
DOI:
10.1016/j.vaccine.2014.09.010
[Indexed for MEDLINE]

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